Gestational diabetes in primiparous women-impact of age and adiposity: a register-based cohort study.

INTRODUCTION: Data on risk factors for gestational diabetes mellitus (GDM) in primiparous women is limited. The aim of this study was to assess the prevalence of GDM and simultaneously evaluate the impact of age and adiposity in primiparous women at risk of GDM risk. MATERIAL AND METHODS: This observational register-based cohort study from the city of Vantaa, Finland, included all 7750 primiparous women giving birth between 2009 and 2015 without previously diagnosed diabetes mellitus. RESULTS: In primiparous women the prevalence of GDM was 16.5% and mean age was 28.2 years (5.2 SD). Primiparous women aged ≥35 years had a significantly higher risk for GDM than women aged <25 years [odds ratio (OR) 2.67, 95% confidence interval (CI) 2.13-3.34]. Primiparous women with a pre-pregnancy body mass index (BMI) ≥30.0 kg/m2 had a significantly higher risk for GDM than women with a pre-pregnancy BMI <25 kg/m2 (OR 5.36, 95% CI 4.53-6.36). The risk of developing GDM showed an increasing trend with increasing age in all BMI categories except the category BMI ≥35 kg/m2 . Normal weight women (BMI 20.0-24.9 kg/m2 ) aged 40 years had a significantly higher risk for GDM than normal weight women aged 28 years (OR 1.48, 95% CI 1.01-2.19). CONCLUSIONS: The prevalence of GDM is high in primiparous women. Both age and degree of adiposity influenced the risk for GDM. To reduce GDM risk, adiposity should be prevented already in childhood and primiparity should be encouraged at a younger age.

Forkhead class O transcription factor 3a activation and Sirtuin1 overexpression in the hypertrophied myocardium of the diabetic Goto-Kakizaki rat.

BACKGROUND: Ventricular remodeling in type 2 diabetes predisposes to fatal coronary heart disease. The proapoptotic forkhead class O transcription factor 3a (FOXO3a) and its modulator, the cardioprotective longevity factor and class III histone deacetylase Sirtuin1 (Sirt1), have been implicated in the regulation of the cardiomyocyte lifespan and hypertrophy. OBJECTIVE: To examine whether FOXO3a-Sirt1 activation is involved in diabetes-induced cardiomyocyte apoptosis and ventricular hypertrophy. METHODS: The blood pressure, cardiac functions, cardiomyocyte size, neurohumoral markers, cardiomyocyte apoptosis, nuclear binding of FOXO3a, and Sirt1 expression were determined for 12-week-old spontaneously diabetic Goto-Kakizaki rats and the nondiabetic Wistar control rats. RESULTS: Goto-Kakizaki rats showed a modest increase in blood pressure, pronounced cardiac hypertrophy, impaired systolic function, and increased plasma brain natriuretic peptide level without changes in plasma renin activity, serum aldosterone or urinary noradrenaline excretion. The cardiomyocyte cross-sectional area was increased by 22%. Phosphorylation of FOXO3a was decreased with a concomitant increase in its nuclear translocation. The myocardial expression of the antiapoptotic FOXO3a modulator Sirt1 was increased two-fold. Acetylation of p53 at the Sirt1-specific lysine 373/382 site was markedly decreased. Myocardial caspase-3 and Bax expression were increased, indicating increased apoptotic signaling; however, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling staining did not reveal any significant increase in cardiomyocyte apoptosis. CONCLUSIONS: Diabetes-induced cardiac remodeling in Goto-Kakizaki rats is associated with cardiac hypertrophy, systolic dysfunction, increased apoptotic signaling and activation of the FOXO3a pathway. The present study also suggests that antiapoptotic Sirt1 protects against cardiomyocyte apoptosis and acts as a novel regulator of cardiomyocyte growth.